Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily.
HNF-4 (hepatocyte nuclear factor 4) is a protein enriched in liver extracts that binds to sites required for the transcription of the genes for transthyretin (TTR), the carrier protein in the serum for vitamin A and thyroid hormone, and for apolipoprotein CIII (apoCIII), a major constituent of chylomicrons and very low-density lipoproteins (VLDL). Synthetic oligonucleotides derived from amino acid sequence of affinity-purified HNF-4 protein (54 kD) were used in the polymerase chain reaction (PCR) to isolate a cDNA clone encoding the protein. HNF-4 is a member of the steroid hormone receptor superfamily with an unusual amino acid in the conserved "knuckle" of the first zinc finger (DGCKG). Studies with in vitro-translated HNF-4 protein show that it binds to its recognition site as a dimer, and cotransfection assays indicate that it activates transcription in a sequence-specific fashion in nonhepatic (HeLa) cells. Northern blot analysis reveals that HNF-4 mRNA is present in kidney and intestine, as well as liver, but is absent in other tissues. DNA-binding and antisera reactivity data suggest that HNF-4 could be identical to liver factor A1 (LF-A1), a DNA-binding activity implicated in the regulation of transcription of the alpha 1-antitrypsin, apolipoprotein A1, and pyruvate kinase genes. The similarity between HNF-4 and other ligand-dependent transcription factors raises the possibility that HNF-4 and the genes it regulates respond to an as yet unidentified ligand.
Sladek
F M
FM
Laboratory of Molecular Cell Biology, Rockefeller University, New York, New York 10021.
Zhong
W M
WM
Lai
E
E
Darnell
J E
JE
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins; D015870:Gene Expression; D051557:Hepatocyte Nuclear Factor 4; D008099:Liver / Q000378:metabolism*; D046911:Macromolecular Substances; D008297:Male; D008969:Molecular Sequence Data; D005810:Multigene Family; D015345:Oligonucleotide Probes; D010750:Phosphoproteins; D051381:Rats; D011919:Rats, Inbred Strains; D011987:Receptors, Steroid / Q000235:genetics*; D011994:Recombinant Proteins / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D051557:Hepatocyte Nuclear Factor 4; D046911:Macromolecular Substances; D015345:Oligonucleotide Probes; D010750:Phosphoproteins; D011987:Receptors, Steroid; D011994:Recombinant Proteins; D014157:Transcription Factors